This study will evaluate a novel strategy for tuberculosis (TB) diagnosis and case finding. Diagnosis of pulmonary TB usually includes analysis of sputum, a viscous material derived from deep in the airways of patients. Sputum is difficult and hazardous to collect, and its viscosity makes it challenging to process, standardize, and analyze. To address the need for an alternative sample type, we hypothesized that some of the Mycobacterium tuberculosis cells that pass through the oral cavity accumulate on the surfaces of oral epithelial cells. Such cells can be collected by using buccal swabs, and detected by using the polymerase chain reaction (PCR) and/or other standard M. tuberculosis detection methods. In a pilot case-control study conducted on samples collected from 20 confirmed TB cases and 20 matched healthy controls, PCR analysis of oral swabs exhibited 90% sensitivity and 100% specificity relative to approved sputum-based methods. The current project will 1) validate these findings in an expanded sample set (N = 107 cases and 107 controls); and 2) enhance the methodology to further improve sensitivity. Oral swab samples are simpler, cleaner, less invasive, less hazardous, smaller volume, and more uniform alternatives to sputum. This approach could enable point of care diagnostic strategies that might not be feasible with sputum. Moreover, because it is non- invasive and does not require active TB symptoms, oral swab analysis could potentially enable active TB case finding. Such a tool would be transformational in TB research, care, and control.